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1.
Protein & Cell ; (12): 214-223, 2014.
Article in English | WPRIM | ID: wpr-757533

ABSTRACT

Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes significantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 (HDAC6), a member of the class II HDAC family, is highly expressed at both protein and mRNA levels in human pancreatic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle progression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 (CLIP-170) and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.


Subject(s)
Humans , Cell Cycle , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Knockdown Techniques , Histone Deacetylase 6 , Histone Deacetylases , Metabolism , Microtubule-Associated Proteins , Metabolism , Neoplasm Proteins , Metabolism , Pancreatic Neoplasms , Metabolism , Pathology , Protein Binding
2.
Protein & Cell ; (12): 150-160, 2011.
Article in English | WPRIM | ID: wpr-757118

ABSTRACT

Angiogenesis, a process by which the preexisting blood vasculature gives rise to new capillary vessels, is associated with a variety of physiologic and pathologic conditions. However, the molecular mechanism underlying this important process remains poorly understood. Here we show that histone deacetylase 6 (HDAC6), a microtubule-associated enzyme critical for cell motility, contributes to angiogenesis by regulating the polarization and migration of vascular endothelial cells. Inhibition of HDAC6 activity impairs the formation of new blood vessels in chick embryos and in angioreactors implanted in mice. The requirement for HDAC6 in angiogenesis is corroborated in vitro by analysis of endothelial tube formation and capillary sprouting. Our data further show that HDAC6 stimulates membrane ruffling at the leading edge to promote cell polarization. In addition, microtubule end binding protein 1 (EB1) is important for HDAC6 to exert its activity towards the migration of endothelial cells and generation of capillary-like structures. These results thus identify HDAC6 as a novel player in the angiogenic process and offer novel insights into the molecular mechanism governing endothelial cell migration and angiogenesis.


Subject(s)
Animals , Chick Embryo , Humans , Mice , Anilides , Pharmacology , Cell Movement , Cell Polarity , Cells, Cultured , Chickens , Endothelial Cells , Cell Biology , Histone Deacetylase 6 , Histone Deacetylases , Metabolism , Physiology , Hydroxamic Acids , Pharmacology , Microtubule-Associated Proteins , Metabolism , Physiology , Neovascularization, Physiologic
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